The present invention provides pharmaceutical compositions and methods, and in particular, vaccines for use in preventing Group A streptococcal infections.
Streptococci are a group of bacteria with the capacity to grow in chains. Many varieties are part of the normal bacterial flora in humans and are not especially harmful. However, a particular group of streptococcal bacteria, called group A and represented by Streptococcus pyogenes, is a human pathogen. Briefly, group A streptococci cause a variety of human illnesses, ranging from uncomplicated pharyngitis and pyoderm a to life-threatening infections associated with toxic shock syndrome, deep tissue invasion and sepsis. In some individuals, untreated streptococcal pharyngitis may be followed by acute rheumatic fever. In recent years there has been a dramatic increase in the incidence of severe streptococcal infections (Davies et al., xe2x80x9cInvasive group A streptococcal infections in Ontario, Canada. Ontario group A Streptoccal study group,xe2x80x9d N. Engl. J. Med. 335:547-554, 1966) and in the incidence of rheumatic fever (Veasey et al., xe2x80x9cResurgence of acute rhematic fever in the intermountain region of the United States,xe2x80x9d N. Eng. J. Med. 316:421-427, 1989).
Although streptococcal infections can be generally treated with antibiotics, in at least 4% of cases the infection leads to acute rheumatic fever. This disease is particularly prevalent in developing countries such as India, where millions of school-age children are affected.
The present invention provides a new Group A streptococcal vaccines with enhanced immunogenicity, and further, provides other related advantages.
Briefly stated , the present invention provides immunogenic synthetic fusion polypeptides which stimulate an immune response against Group A streptococci. Within one aspect such polypeptides comprise (a) at least two immunogenic polypeptides from a Group A streptococci of at least 10 amino acids in length which are capable of stimulating an immune response against Group A streptococci, and a peptide C terminal to the immunogenic polypeptide which protects the immunogenicity of the immunogenic portion. Within preformed embodiments, the C-terminal peptide is not required to stimulate an immune response against Group A streptococci and hence, may be an inconsequential non-immunogenic peptide, or a reiterated immunogenic polypeptide. Within certain embodiments, the immunogenic polypeptide can be obtained from a wide variety of Group A streptococci (ranging from xe2x80x9c1xe2x80x9d to greater than xe2x80x9c90xe2x80x9d), including for example, Types 1, 1.1, 2, 3, 4, 5, 6, 11, 12, 13, 14, 18, 19, 22, 24, 28, 30, 48, 49, 52, 55 and 56.
Within other aspects of the present invention, vaccinating agents are provided for promoting an immune response against Group A streptococci, comprising (a) at least two immunogenic polypeptides from a Group A streptococci of at least 10 amino acids in length which are capable of stimulating a protective immune response against Group A streptococci, and (b) a peptide C terminal to the immunogenic polypeptide which protects the immunogenicity of the immunogenic portion, wherein the C-terminal peptide is not required to stimulate an immune response against Group A streptococci. As above, the polypeptide may be selected from a wide variety of Group A streptococci (ranging from xe2x80x9c1xe2x80x9d to greater than xe2x80x9c90xe2x80x9d), including for example, types 1.1, 2, 3, 4, 5, 6, 11, 12, 13, 14, 18, 19, 22, 24, 28, 30, 48, 49, 52, 55 and 56. Within certain further embodiments, the vaccinating agent may further comprise an adjuvant, such as, for example, alum, Freund""s adjuvant, and/or an immunomodulatory cofactor e.g., (IL-4, IL-10, xcex3-IFN, or IL-2, IL-12 or IL-15).
Also provided are methods for vaccinating a host against Group A streptococci infections, comprising administering a vaccinating agent as described above.